Estradiol administration mediates the inflammatory response to formalin in female rats.

Female rats demonstrate higher pain sensitivity than do males in various nociceptive assays of inflammation. In the present study, we found that estradiol (20%) replacement in ovariectomized rats attenuated the chronic phase of the formalin response but only at high formalin concentrations thought to rely on peripheral inflammation. An inactive isomer of estradiol, alpha-estradiol, failed to result in the same attenuation (P > 0.05). Our results suggest that estradiol's actions in inflammatory responses are mediated through genomic estrogen receptor-mediated mechanisms.